Hantavirus Pulmonary Syndrome is a rare and severe viral respiratory infection. It starts with flu-like symptoms like fever and body aches and progresses into lung edema, respiratory failure, and death.

What is Hantavirus Pulmonary Syndrome?

Hantavirus pulmonary syndrome is the predominant disease caused by the Hantavirus genus of viruses in North and South America. It is a widespread infection that primarily affects the respiratory system, rapidly compromises blood circulation, and can quickly cause death.¹

Causative Agent for Hantavirus Pulmonary Syndrome

Hantaviruses or ortho-hantaviruses are a type of virus that cause asymptomatic infections in mammals. However, when they affect humans, they cause diseases such as Hantavirus pulmonary syndrome and Hantavirus hemorrhagic fever with renal syndrome. These viruses are named after the Hantan River in South Korea, where their first species was discovered.
Among the Hantaviruses, the most common causative agent for hantavirus pulmonary syndrome is the Sin Nombre virus, which results in the highest number of disease cases in the United States and Canada. Other Hantaviruses that cause the disease include:

Andes virus
Black Creek Canal virus
New York virus
Bayou virus²

Causes of Hantavirus Pulmonary Syndrome Transmission

Hantavirus pulmonary syndrome is caused by the transmission of a Hantavirus from animals to humans. It is transmitted through close contact with fluids or droppings of a rodent that has been infected with Hantavirus.

Modes of Transmission:

Hantavirus pulmonary syndrome is a zoonotic disease, which means it gets transmitted from animals to humans and from humans to humans. This transmission can occur through many different routes.

Airborne Transmission

Hantavirus is most commonly transmitted when infected aerosols are inhaled by humans. Aerosols are small, infected particles carried in the air. These are formed and released into the air when an infected rodent urinates or defecates.

Direct Physical Contact

Handling or coming into accidental contact with a rodent that is infected with Hantavirus can also transmit the infection to you. Transmission offer occurs when people touch their mucous membranes afterward, such as those in the nose, eyes, or mouth. Rodents can also transmit the virus through their saliva, as a considerable number of cases stem from rodent bites.

Contamination of Food & Water

Eating food or drinking water that has been contaminated with the feces or urine of an infected rodent causes the transmission of the Hantavirus. This can happen in campsites as well as neighborhoods where mice and rats are common.

Human-to-Human Transmission

Certain strains of the Hantaviruses, such as the Andes virus from South America, can also be transmitted among humans. As with rodents, this transmission is usually through close contact with the body fluids of an affected individual.

Risk Factors:

The risk of contracting hantavirus pulmonary syndrome increases with certain lifestyle choices, such as:

Living in areas where there is a huge population of rodents
Living in rural or semi-rural areas
Camping and hiking frequently
Working in the woods
Working in farming and construction
Having poor hygiene³

Symptoms of Hantavirus Pulmonary Syndrome

Hantavirus pulmonary syndrome initially presents as a flu-like illness. However, it rapidly progresses into more life-threatening clinical features such as respiratory failure and vascular compromise. The signs and symptoms can be divided into a number of phases, such as:

Incubation Phase:

Symptoms don’t appear right away, as a hantavirus enters an incubation period right after exposure. This incubation phase is 1 to 5 weeks long and lets the virus silently replicate in the blood vessels in your respiratory system.

Prodromal Phase:

The incubation phase is followed by a prodrome of flu-like symptoms, which lasts from 3 to 6 days. These symptoms include:

Fever which is usually above 101°F
Chills and shivering
Severe muscle pain in large muscles such as those of the thighs, back and shoulders
Severe fatigue
Generalized weakness
Nausea and vomiting
Abdominal discomfort
Headache
Dizziness

Cardiopulmonary Phase:

Cardiopulmonary symptoms emerge suddenly after the prodromal phase when the virus has dealt considerable damage to lung vasculature. Fluid leaks into the lungs and causes edema, as well as a variety of symptoms:

Severe respiratory distress
Fast, shallow breathing
Non-productive cough
Pulmonary edema
Low blood pressure
Increased heart rate
Respiratory failure
Shock

prodromal phase of hantavirus pulmonary syndrome — Cardiopulmonary symptoms emerge suddenly after the prodromal phase when the virus has dealt considerable damage to lung vasculature.

The mortality in this phase can be over 40%, so you require immediate and intensive management in a hospital setting.

Diuretic Phase:

After the cardiopulmonary phase, the body starts to rid itself of the excessive fluid buildup. During this phase, the symptoms include:

Increased urination
Increased sweating
Fatigue
Weakness
Dehydration
Electrolytes imbalance⁴

Complications of HPS

Hantavirus pulmonary syndrome is a serious condition and is usually complicated by a plethora of symptoms, such as:

Acute respiratory failure
Acute kidney injury
Thrombocytopenia
Coagulopathy
Arrhythmia
Hypotensive shock⁵

How is a Hantavirus Pulmonary Syndrome Diagnosis Confirmed?

Since the symptoms of hantavirus pulmonary syndrome mimic those of many other respiratory illnesses and viral infections, a thorough workup is required to confirm its diagnosis. Diagnosis is established through both medical examination and tests.
The gold standard for confirming the diagnosis of hantavirus pulmonary syndrome is enzyme-linked immunosorbent assay or ELISA, alongside a triad of three laboratory findings:

A low platelet count
An increased number of white blood cells, most of which are immature white blood cells
Presence of immunoblasts in the blood

History & Physical Exam:

Doctors specifically ask about rodent exposure, as rodents are the hosts that transmit the hantavirus to humans. They will ask you if you have come into contact with any animal droppings or body fluids, especially if you live in a rural area or have been camping in a forest.
In addition to a detailed history, doctors look for signs on your physical examination, such as:

Fine, crackling sounds in your lungs during inspiration which indicate fluid buildup
High-pitched whistling in your lungs during expiration indicates airway narrowing
A scratching sound called the ‘pleural rub’ which refers to the inflammation of the pleura

In addition to respiratory findings, your doctor may also find an increased heart rate as well as abnormal heart sounds.

Lab Investigations:

A number of specific laboratory tests confirm or point towards the presence of hantavirus in your body, including:

ELISA for Hantavirus detects antibodies that your immune system has produced against the Hantavirus infection
Polymerase chain reaction or PCR detects the presence of genetic material from the hantavirus in your blood
Immunofluorescence assays detect the antigens of hantaviruses present in different tissues of your body

ELISA is the gold standard investigation for the diagnosis of HPS.

In addition to strictly diagnostic tests, a number of additional tests are performed when a doctor suspects you might have hantavirus pulmonary syndrome, such as:

A complete blood count or CBC test will show a low platelet count and a high white blood cell count
Renal function tests show the health of kidneys through creatinine and urea levels, which are often affected because of cardiovascular compromise in Hantavirus syndrome
Derangement in liver function tests will show the involvement of multiple organs due to severe disease
Serum electrolytes, as well as random blood sugar, let doctors determine what type of fluid can be administered to you, as dehydration and electrolyte imbalance are common features of Hantavirus pulmonary syndrome

Radiological Imaging:

A number of radiological Imaging modalities are employed to check for hallmark changes caused by hantavirus pulmonary syndrome in your body. These include:

Chest X-ray scans are the first radiological imaging performed while investigating hantavirus infections. They help doctors determine if your symptoms have a respiratory or cardiac cause. Chest X-ray findings in hantavirus pulmonary syndrome often include cloud-like opacities, which show pulmonary edema, or infiltrates that indicate the presence of fluid in your lungs.
High-contrast computerized tomography or HRCT scans show the structure of the lungs in greater detail than chest radiographs. In hantavirus pulmonary syndrome, they often showcase hazy opacities (fluid or inflammation), thickened walls between different lung sections (increased fluid because of infection), and thickening of the walls of the bronchi, which are the parts of the respiratory tract present before the lungs.

Treatments for Hantavirus Pulmonary Syndrome

Hantavirus pulmonary syndrome requires immediate management in an intensive care setting. There is no known cure, so the treatments are supportive and help your immune system manage the symptoms and complications of the disease til your body can recover from it.

Oxygen Therapy

Since hantavirus causes a buildup of fluid in the lungs, which stops your body from getting enough oxygen, administering oxygen is the go-to treatment for hantavirus pulmonary syndrome. Doctors aim to keep your arterial oxygen saturation above 90% at all costs. They will use several options for this, depending on the severity of the disease:

Nasal cannula
Oxygen mask
High-flow nasal oxygen
Noninvasive ventilation

Fluid Replacement

Hantavirus pulmonary syndrome causes your capillaries to “leak,” which results in the accumulation of body fluids in your cavities yet lowers them in your bloodstream. For this reason, it is important to carefully replace the displaced fluids so that you don’t go into hypovolemic shock — a compromise in your blood circulation that can cause organ failure and death. The fluids most commonly used for hantavirus pulmonary syndrome are normal saline and ringer’s lactate.

Blood Pressure Medication

A number of blood pressure-regulating drugs are used in the management of Hantavirus pulmonary syndrome. They improve the functioning of your heart and help it pump more blood to your vital organs, such as:

Vasopressors
o Norepinephrine (first line)
o Epinephrine
o Dopamine
Inotropes
o Dobutamine

Antivirals

As of 2024, no antiviral drugs have been approved for the treatment of hantavirus pulmonary syndrome. However, research efforts have been focused on a few options:

Ribavirin — interferes with viral replication
Favipiravir — interferes with viral replication
Monoclonal antibodies — artificially produced antibodies that mimic the action of your immune system
Interferons — artificially produced copies of interferons, which are proteins that defend the body against viral infections

Mechanical Ventilation

When noninvasive methods of ventilation cannot help you maintain enough oxygen in your blood, or you’re facing severe hantavirus pulmonary syndrome complications, mechanical ventilation is used to help you breathe better.
Doctors attach a ventilator machine to your body, which assists your breathing. As you get better, doctors slowly reduce the support and check if you can breathe on your own.⁶

Prognosis

Hantavirus pulmonary syndrome carries a 40% mortality even with treatment, making its prognosis guarded. The disease also has no known cure, and the only available management is supportive care to help your body fight the infection on its own. In addition, the death rate is high even in young, otherwise healthy individuals.⁷

Why is Hantavirus so deadly?

HPS has one of the highest mortality rates for all respiratory illnesses despite its rarity. This makes hantavirus one of the deadliest viruses known to humans. It causes severe, progressive disease, which is so rapid that it can be impossible for your immune system to find back.
In addition, instead of breaking down cells directly, it causes leakage of fluid through cell signaling, which causes severe disease after a seemingly harmless prodromal period. It also triggers a huge host immune response, due to which the body’s immune system releases a dangerously high number of inflammatory chemicals known as cytokines.
This “cytokine storm,” which is actually your body’s attempt to fight against the hantavirus, unfortunately, results in damage to your own organ and causes rapid shutdown of a number of your vital organs. In addition, scientists have been unable to develop a vaccine for the hantavirus because of its complex genome and surface structure. All of these attributes make hantavirus pulmonary syndrome extremely deadly.⁸

Conclusion

Hantavirus pulmonary syndrome is a rare but rapidly progressive and deadly respiratory infection caused by Hantaviruses. The infection begins with flu-like prodromal symptoms such as fever, malaise, and cough. However, it soon morphs into severe respiratory distress and cardiovascular compromise and can result in multiorgan failure. Patients require round-the-clock care in intensive care settings for a chance at recovery. Even then, around 40% of patients die from the disease. There is no vaccine or cure for the hantavirus, and disease management is focused on providing supportive care to your body so that it can recover from the virus on its own.

Refrences

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Yuill, T. M. (2023, June). Hantavirus Infection. MSD Manual Professional Edition; MSD Manuals. https://www.msdmanuals.com/professional/infectious-diseases/arboviruses-arenaviridae-and-filoviridae/hantavirus-infection
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Hantavirus Pulmonary Syndrome: Causes, Risks & Prevention

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